There is an increasing potential for human exposure and potential health risks to cyanide through water as our drinking water supplies become increasingly contaminated. Increasing manufacturing, landfills and disposal sites, and mining activities have increased the cyanide content of our water. Cyanide contaminated water also poses health problems to wildlife populations. A particular source of wildlife health risk is associated with cyanide contaminated heap leach and tailings ponds from precious metal mining operations, to migratory birds. This proposal is designed to study the potential health effects of acute and intermediate exposure periods to sublethal levels of cyanide through drinking water. We will study both a mammalian (Wistar rat) and avian (mallard duck) specie. Initially, cyanide exposure for acute and intermediate time periods will be used to assess specie cyanide tolerance. Subsequently, non-lethal doses will be used to assess cyanide induced oxidative stress and mitochondrial damage. Oxidative stress will be determined by monitoring various biochemical markers for oxidative stress such as the antioxidant enzymes, tissue glutathione levels and lipid peroxidation. Heart, liver and brain tissues will be tested as these are target tissues for cyanide toxicity. Mitochondrial function and integrity will be assessed from mitochondria isolated from these same tissues. Respiratory control ratios (RCR's) and cytochrome oxidase activity will be used as determinants of mitochondrial function. Rhodanese activity and tissue ATP levels will also be assessed. Tissue and mitochondrial CN concentrations will be measured following both acute and intermediate exposures. Mn SOD will be for its potential as a biochemical marker of cyanide exposure. It is anticipated that these studies will serve as a model and database for future studies of environmental mitochondrial poisons and their interactions with heavy metals.